Results from a phase I safety trial of hAADC gene therapy for Parkinson disease

Neurology. 2008 May 20;70(21):1980-3. doi: 10.1212/01.wnl.0000312381.29287.ff. Epub 2008 Apr 9.


Background: In a primate model of Parkinson disease (PD), intrastriatal infusion of an adeno-associated viral (AAV) vector containing the human aromatic l-amino acid decarboxylase (hAADC) gene results in robust gene expression. After gene transfer, low doses of systemically administered l-dopa are converted to dopamine in the transduced striatal neurons, resulting in behavioral improvement without the side effects typically associated with higher doses of l-dopa. These studies led to the initiation of a phase I safety trial. Here we report the findings for the first cohort of five patients.

Methods: Patients with moderate to advanced PD received bilateral infusion of a low dose of the AAV-hAADC vector into the putamen. PET scans using the AADC tracer, 6-[18F]fluoro-l-m-tyrosine (FMT), were performed at baseline and at 1 and 6 months after infusion as an in vivo measure of gene expression.

Results: PET results showed an average 30% increase in FMT uptake (K(i)(c)) in the putamen after gene transfer. Preliminary analysis of clinical data indicates a modest improvement, but absence of a control and the nonblinded analyses make interpretation difficult.

Conclusions: Thus far, this gene therapy approach has been well tolerated and shows PET evidence of sustained gene expression. These initial findings demonstrate the safety of the therapy; higher doses of adeno-associated viral vector containing the human aromatic l-amino acid decarboxylase gene in the next cohort of patients may further increase dopamine production in the putamen and provide more profound clinical benefit.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aromatic-L-Amino-Acid Decarboxylases / genetics*
  • Female
  • Gene Expression
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Treatment Outcome


  • Aromatic-L-Amino-Acid Decarboxylases